The present invention relates to diagnostic methods for detecting or evaluating the presence of periodontal diseases (especially gingivitis) in humans or lower animals by measuring the presence of leukocyte esterase. The present invention further relates to diagnostic products and diagnostic kits useful for detecting or evaluating the presence of periodontal diseases (especially gingivitis) in humans by utilizing agents which detect the presence of leukocyte esterase.
Periodontal diseases, such as, for example, periodontitis, gingivitis, stomatitis, and the like, are inflammatory conditions of the mouth characterized by inflammatory oral tissue changes usually due to local irritation. The destructive inflammatory process involves the interaction between bacteria, food debris, oral leukocytes, and the epithelial attachment around the tooth and periodontal membranes. If allowed to progress unchecked, such inflammatory processes can lead to resorption of the supportive bone around the roots of the teeth and eventual loss of teeth. The early detection of such inflammatory conditions is very important to proper dental treatment.
It has been known for many years that at local sites of inflammation the body produces an increased number of leukocytes. References have suggested measuring the presence of leukocytes for evaluating periodontal health, for example: Rams et al., "A Rationale for Management of Periodontal Diseases: Rapid Identification of Microbial `Therapeutic Targets` with Phase-Contrasts Microscopy", JADA, 106, pages 803-812 (1983); and Rams et al., "A Rationale for the Management of Periodontal Diseases: Effects of Tetracycline on Subgingival Bacteria", JADA, 107, pages 37-41 (1983); the disclosure of both these articles being incorporated herein by reference in their entirety.
In addition, diagnostic methods for detecting the presence of the inflammatory periodontal disease condition have been developed based on detecting peroxidase enzymes from polymorphonuclear (PMN) leukocytes as described, for example, in "Diagnostic Method for Detecting Periodontal Disease", European Patent Application Publication No. 158796, by Richardson-Vicks Inc., published Oct. 23, 1985, the disclosure of which is incorporated herein by reference in its entirety. Reagents for assessing periodontal diseases by detecting the presence of peroxidases and/or salivary occult blood in the oral cavity are known, having been described in: Tenovuo and Anttonen, "Application of a Dehydrated Test Strip, HEMASTIX.RTM., for the Assessment of Gingivitis", J. of Clinical Periodontology, 5, pages 206-212 (1978); Anttonen et al., "Experimental Gingivitis in Man Determined by Various Indices with Special Reference to HEMASTIX.RTM.-Strip Index", Proc. Finn. Dent. Soc., 74, pages 41-45 (1978); Ueda et al., "Assessment of Gingival Bleeding with a Salivary Occult Bleeding Test Strip", Bull. Josai Dent. Univ., 13 (3), pages 628-633 (1984); Yamaoka et al., "Relation between Changes in the Clinical Symptoms in the Value of Salivary Occult Blood Tests in Periodontally Involved Patients--A Study Using a Test Paper for Saliva Examination (Salivaster Bld)", Nippon Shishubyo Gakkai Kaishi, 27, (4), pages 912-922 (1985); and Smith et al., "Changes in Salivary Peroxidase Activity Observed During Experimentally-Induced Gingivitis", J. Clin. Periodontol. (Denmark), 11, (6), pages 373-378 (1984); the disclosures of all these publications being incorporated herein by reference in their entirety.
Thus, while there has been much research into methods for detecting periodontal diseases, none of these references disclose or discuss measuring leukocyte esterase as a method for detecting periodontal diseases. In fact, one publication relating to the use of reagent strips to indicate the presence of leukocyte esterase in urine for detecting whether a patient has pyuria (Kusumi et al., JAMA, 245 (16), pages 1653-1655 (1981); the disclosure of which is incorporated herein by reference in its entirety) specifically speculates that the leukocyte esterase test "cannot, however, be used to test sputum, since saliva is rich in esterase activity." Therefore, the present invention is clearly surprising in light of the published literature.
An object of the present invention is to provide methods for detecting the presence of periodontal diseases (especially gingivitis) in humans or lower animals. Another object is to provide methods for evaluating the severity of periodontal diseases (especially gingivitis) in humans or lower animals. An object of the present invention is also to provide methods for following diseased gingival sites for improvement during the course of therapy; and for targeting gingival sites that are susceptible to gingivitis, prior to overt inflammation, for further monitoring or preventative treatment. A further object is to provide diagnostic products useful in vivo for detecting or evaluating the presence of periodontal diseases in humans. A still further object is to provide diagnostic kits useful for detecting or evaluating the presence of periodontal diseases in humans.
These and other objects of the present invention will become readily apparent from the detailed description which follows.
All percentages and ratios used herein are by weight unless otherwise specified.